The present invention relates to a method for the enzymatic esterification reaction. More particularly, the invention relates to an enzymatic esterification reaction of a primary terpene alcohol having a chiral atom and a carboxylic acid as the substrates with an object of racemic resolution, which is industrially important in the organic syntheses, in a high yield and good stereoselectivity.
Certain primary terpene alcohols such as citronellol have chirality and are obtained usually as a racemic compound. In view of the specific biological activity exhibited by each of the optical isomers constituting a racemic compound, it is sometimes desirable to obtain one of the optical isomers by the racemic resolution of the racemic compound. Needless to say, racemic resolution of a racemic compound is generally impossible by an ordinary organic reaction while a possibility of racemic resolution could be expected by a biochemical reaction such as enzymatic reactions.
While stereoselective enzymatic reactions have been reported for the stereoselective synthesis of certain secondary terpene alcohols such as menthol and borneol in an organic solvent such as n-hexane and isooctane in the presence of a lipase, no attempts to cause an enzymatic stereoselective reaction involving a primary terpene alcohol such as citronellol have been successful even by undertaking the same reaction conditions as in the enzymatic reaction for the secondary terpene alcohols.
Turning now to the problem on the reaction medium for biochemical reactions, organic solvents as a reaction medium are highlighted in recent years for various biochemical reactions and number of the cases is increasing year by year for the industrial utilization of biochemical reactions conducted in an organic solvent. One of the objects to use an organic solvent as the reaction medium is to achieve high homogeneity of the reaction mixture as compared with a conventional aqueous reaction medium especially when the solubility of a reactant compound involved is low in an aqueous medium. Use of an organic solvent as a medium for an enzymatic reaction, however, sometimes has a problem that the enzyme is denaturated eventually resulting in deactivation or loss of the enzymatic specificity since the higher-order structure of the enzyme is destroyed as a consequence of the unduly enhanced affinity between the solvent molecules and the hydrophobic groups in the enzyme molecules. Accordingly, it is eagerly desired to develop a reaction medium for an enzymatic biochemical reaction in which oil-soluble or water-insoluble reactant compounds can be readily dissolved while the higher-order structure of the enzyme molecules can be kept intact even by contacting with the medium, for example, in an enzymatic reaction involving a primary terpene alcohol having chirality by which racemic resolution of the racemic compound could be expected as a possibility.